Pigment epithelial detachment followed by retinal cystoid degeneration leads to vision loss in treatment of neovascular age-related macular degeneration

Abstract

Purpose: Intravitreal antiangiogenic therapy is the major therapeutic breakthrough in neovascular age-related macular degeneration (AMD). Optical coherence tomography (OCT) is the leading diagnostic tool, but solid criteria for optimal therapeutic outcomes are lacking. A comprehensive analysis of structure/function correlations using Food and Drug Administration- and European Medicines Agency-approved substances and fixed and flexible regimens was performed.

Design: Post hoc analysis of a prospective, randomized multicenter clinical trial including 189 study sites.

Participants: A total of 1240 patients with active neovascular AMD.

Methods: Participants received intravitreal ranibizumab or aflibercept. A fixed regimen was used for 48 weeks followed by a flexible regimen until week 96. At monthly intervals, best-corrected visual acuity (BCVA) was measured and retinal morphology was assessed by standardized OCT, including intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachment (PED), presenting with a width ≥400 μm or a height of ≥200 μm. Results were correlated for each regimen, feature, and time.

Main outcome measures: The BCVA outcomes in relation to retinal pathomorphology based on noninferiority for all treatment arms.

Results: In neovascular AMD, only IRC at baseline and persistent through week 12 had a negative impact on BCVA. With therapeutic intervention, exudative features such as IRC and SRF resolved rapidly in 74% of eyes, whereas PED responded only slowly with 38%. Independent of the type of regimen, fixed or flexible, retinal morphology correlated tightly with visual function. Intraretinal cysts consistently showed the lowest BCVA gains with either regimen or substance. With the switch from a fixed to a flexible pro re nata (PRN) regimen, progressive visual loss occurred exclusively in the group with primary PED presenting as the hallmark of neovascular activity and was induced by secondary formation of IRC in the neurosensory retina.

Conclusions: The efficacy of antiangiogenic therapy in neovascular AMD is strongly determined by morphologic features. The subretinal pigment epithelium lesion underlying PED appears to be the primary indicator for progressive disease activity, whereas secondary cystoid degeneration is the most relevant imaging marker for visual function. Clinically, PED emerged as trigger for consecutive vision loss in PRN treatment.